The main objectives of this proposal are the following: (a) To determine whether or not stimulation of central catecholaminergic system induces cerebral edema through the action of released catecholamines on blood-brain barrier and its effect of the transport of water and electrolytes in Reye's syndrome. (b) To determine whether cerebral edema causes and increase in peripheral sympathetic tone and establish whether or not the measurement of plasma catecholamines is an adequate method to study the rapidly occuring changes in sympathetic tone following intracranial hypertension in Reye's syndrome. (c) To determine whether differences between patients with Reye's syndrome and controls in the level of mitochondrial MAO result from variation in number of enzyme molecules or from variation in their catalytic activity. Furthermore, the possibility that MAO activity is reduced as a result of the presence of specific inhibitor(s) in the plasma or urine of these patients will also be studied. (d) To determine whether or not electron micrography of platelet mitochondria reveals ultrastructural changes that serve as a specific criteria in the diagnosis of Reye's syndrome. The Reye's syndrome patients selected for the studies outlined in this proposal are those admitted to three major medical centers: Egleston Children's Hospital of Emory University, Atlanta, GA; Children's Medical Center of Wright State University, Dayton, OH; and, Children's Hospital Medical Center of University of Cincinnati, Cincinnati, OH. The findings that will be derived from these studies will not only shed light on the mechanism of cerebral edema of Reye's syndrome but may provide us with safe and convenient ways of confirming the diagnosis of the disease, monitoring of intracranial pressure and the possibility of identifying a susceptible population that may be vulnerable to develop Reye's syndrome.
| Faraj, B A; Cragoe Jr, E J; Sarper, R et al. (1988) Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711. Life Sci 42:2429-37 |
| Sarper, R; Tarcan, Y; Malveaux, E et al. (1987) Quantitative evaluation of brain edema by radionuclide imaging technique. J Pharm Sci 76:21-4 |
| Faraj, B A; Caplan, D; Lolies, P et al. (1987) Salicylate and mitochondrial monoamine oxidase function in Reye's syndrome. J Pharm Sci 76:423-6 |
| Faraj, B A; Schmidt, F H; Sarper, R et al. (1987) Tyramine neurotoxicity and first-pass brain technetium-99m-diethylenetriamine penta-acetic acid. J Pharmacol Exp Ther 241:42-7 |
| Faraj, B A; Newman, S L; Caplan, D B et al. (1985) Platelet-monoamine oxidase activity in Reye's syndrome. J Pediatr Gastroenterol Nutr 4:532-6 |
